U.S. patent application number 11/935824 was filed with the patent office on 2008-06-12 for measuring analyte concentrations in liquids.
Invention is credited to David B. Blackford, Derek R. Oberreit, Frederick R. Quant.
Application Number | 20080137065 11/935824 |
Document ID | / |
Family ID | 39365339 |
Filed Date | 2008-06-12 |
United States Patent
Application |
20080137065 |
Kind Code |
A1 |
Oberreit; Derek R. ; et
al. |
June 12, 2008 |
Measuring Analyte Concentrations in Liquids
Abstract
A high performance liquid chromatography system employs a
nebulizer with a flow restriction at the exit of its mixing chamber
to produce finer droplets, and an adjustable impactor for increased
control over droplet sizes. Downstream of the mixing chamber, the
nebulizer can incorporate tubing that is permeable to the sample
liquid, to promote aerosol drying through perevaporation. A
condensation particle counter downstream of the nebulizer uses
water as the working medium, and is adjustable to control threshold
nucleation sizes and droplet growth rates. A particle size selector
employing diffusion, electrostatic attraction or selection based on
electrical mobility, is advantageously positioned between the
nebulizer and the CPC.
Inventors: |
Oberreit; Derek R.;
(Roseville, MN) ; Quant; Frederick R.; (Shoreview,
MN) ; Blackford; David B.; (North Oaks, MN) |
Correspondence
Address: |
HAUGEN LAW FIRM
SUITE 1130 - TCF TOWER, 121 SOUTH EIGHTH STREET
MINNEAPOLIS
MN
55402
US
|
Family ID: |
39365339 |
Appl. No.: |
11/935824 |
Filed: |
November 6, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60857609 |
Nov 7, 2006 |
|
|
|
Current U.S.
Class: |
356/37 ;
261/78.1; 73/53.01 |
Current CPC
Class: |
G01N 30/84 20130101;
G01N 2030/8447 20130101; G01N 15/065 20130101 |
Class at
Publication: |
356/37 ;
261/78.1; 73/53.01 |
International
Class: |
G01N 1/00 20060101
G01N001/00; B01D 47/00 20060101 B01D047/00; G01N 30/00 20060101
G01N030/00 |
Claims
1. A system for measuring analyte concentrations in liquids,
including: an analyte separation stage adapted to separate
different analytes in a liquid sample primarily into different
regions within the liquid sample, thereby to produce a separation
stage output in which a plurality of different analytes are so
separated; a nebulizing stage downstream of the analyte separation
stage adapted to generate an aerosol stream composed of droplets of
the separation stage output suspended in a carrier gas; an
evaporation stage downstream of the nebulizing stage adapted to
substantially evaporate the liquid, whereby the aerosol leaving the
evaporation stage is composed of residue particles of the different
analytes suspended in the carrier gas; a saturation stage disposed
downstream of the evaporation stage, maintained substantially at a
first temperature, and adapted to merge the aerosol with a working
medium vapor having a mass diffusivity higher than a thermal
diffusivity of the carrier gas, to substantially saturate the
aerosol with the working medium vapor; a condensation stage
disposed downstream of the saturation stage, maintained at a second
temperature above the first temperature, and adapted to merge
further working medium vapor with the substantially saturated
aerosol to supersaturate the aerosol and thereby cause droplet
growth through condensation of the working medium onto the residue
particles; and a sensing stage downstream of the condensation stage
adapted to optically sense the droplets and generate electrical
signals useful in indicating analyte concentrations.
2. The system of claim 1 wherein: the analyte separation stage
comprises a liquid chromatography column adapted to cause different
non-volatile analytes to travel through the chromatography column
at respective different rates as the liquid sample progresses
through the column, whereby the different regions exit the
chromatography column at different times.
3. The system of claim 2 further including: an information
processing stage coupled to the sensing stage to receive the
electrical signals and generate analyte concentration information
based on the electrical signals.
4. The system of claim 3 wherein: the aerosol stream includes
temporally separated portions corresponding to the different
regions exiting the chromatography column, whereby the
corresponding electrical signals and analyte concentration
information indicate different concentrations individually
associated with different analytes.
5. The system of claim 1 wherein: the evaporation stage comprises a
heating element for heating the aerosol to facilitate evaporation
of the liquid.
6. The system of claim 1 wherein: the saturation stage and
condensation stage comprise, respectively, a saturation region and
a supersaturation region of a condensation particle counter.
7. The system of claim 6 further comprising: a first temperature
maintenance component adapted to maintain the first temperature
along the saturation region, and a second temperature maintenance
component adapted to maintain the second temperature along the
supersaturation region.
8. The system of claim 7 wherein: the first and second temperature
maintenance components are adjustable to selectively vary the first
temperature, the second temperature, and a difference between said
temperatures.
9. The system of claim 6 further including: a holding component
disposed along the saturation region and the supersaturation region
adapted to receive the working medium in liquid form and release
the working medium in vapor form to the aerosol along the
saturation and condensation stages.
10. The system of claim 1 wherein: the sensing stage comprises a
coherent energy beam intersecting the aerosol stream and a
photodetector disposed proximate the aerosol stream to detect
alterations or interruptions in transmission of the coherent energy
as the droplets intersect the beam.
11. The system of claim 10 wherein: the sensing stage further
comprises a photometric detector for measuring an amplitude of the
coherent energy scattered simultaneously by pluralities of the
droplets.
12. The system of claim 1 further including: a particle selection
stage disposed between the evaporation stage and the saturation
stage, adapted to selectively remove from the aerosol particles
having sizes less than a predetermined threshold.
13. The system of claim 12 wherein: the selection stage is adapted
to electrostatically remove the particles.
14. The system of claim 1 further including: means for moving the
aerosol through the saturation stage and the condensation stage in
a substantially laminar flow.
15. The system of claim 1 wherein: the carrier gas consists
essentially of air, and the working medium consists essentially of
water.
16. The system of claim 1 further including: means for introducing
a dry gas along the evaporation stage for merger with the aerosol
to sustain evaporation of the liquid.
17. A process for configuring the system of claim 3 to minimize
erroneous counts due to increases in residue particle
concentration, including: while testing the system with different
particle challenges of known particle sizes and concentrations,
generating a plurality of voltages V.sub.DT indicating
discriminator time and individually associated with the different
challenges; using the information processing stage to store an
operative linkage associating the discriminator time voltage levels
V.sub.DT and the corresponding particle concentrations; and
configuring the information processing stage to generate a
corresponding output indicating a particle concentration responsive
to receiving an electrical signal corresponding to a given
discriminator time voltage level V.sub.DT.
18. A system for analyzing liquids, including: an analyte separator
adapted to separate different analytes in a liquid sample primarily
into different regions within the liquid sample, thereby to produce
a separator output in which a plurality of different analytes are
so separated; a nebulizer fluid coupled to receive at least a
portion of the separator output, and to generate an aerosol
composed of droplets of the liquid suspended in a carrier gas; a
conduit structure for guiding travel of the aerosol in an aerosol
stream away from a merger zone of the nebulizer, wherein at least a
portion of the conduit structure is permeable to the liquid to
promote an evaporation of the liquid and migration of the vapor
through said portion of the conduit to an exterior thereof as the
aerosol is conveyed along the conduit structure, whereby the
aerosol leaving the conduit structure is composed of residue
particles of the analytes suspended in the carrier gas; and a
concentration indicating component disposed to receive the aerosol
leaving the conduit structure and adapted to indicate analyte
concentration based on the residue particles received.
19. The system of claim 18 wherein: the concentration indicating
component comprises a droplet growth component disposed downstream
of the conduit structure to receive the aerosol and merge the
aerosol and a working medium vapor to supersaturate the aerosol and
thereby cause droplet growth through condensation of the working
medium onto the residue particles; and a droplet sensing component
downstream of the condensation component adapted to optically
detect the droplets and generate electrical signals indicating
analyte concentrations.
20. The system of claim 18 wherein: the droplet growth component
comprises a saturation stage adapted to merge the aerosol and the
working medium vapor to substantially saturate the aerosol with the
working medium vapor, and condensation stage downstream of the
saturation stage and maintained at a condensation stage temperature
different from the saturation stage temperature to merge further
working medium vapor and the substantially saturated aerosol to
supersaturate the aerosol and thereby cause growth of the droplets
through condensation of the working medium onto the residue
particles.
21. The system of claim 18 wherein: the droplet growth component
comprises a first conduit for conveying aerosol at a first
temperature, a second conduit for conveying a gas saturated with a
working medium vapor at a second temperature higher than the first
temperature, and a droplet growth region fluid coupled to the first
and second conduits to merge the aerosol and the saturated gas to
achieve supersaturation and resulting droplet growth through
condensation of the working medium onto the aerosol particles.
22. A system for analyzing liquid samples, including: an analyte
separator adapted to separate different analytes in a liquid sample
primarily into different regions within the liquid sample, to
produce a separator output in which a plurality of different
analytes are so separated; a nebulizer fluid coupled to receive at
least a portion of the separator output in a merger zoned thereof
and to generate an aerosol composed of droplets of the liquid
suspended in a carrier gas; an evaporation stage downstream of the
nebulizer adapted to substantially evaporate the liquid whereby the
aerosol leaving the evaporation stage is composed of residue
particles of the different analytes suspended in the carrier gas;
an electrostatic selector disposed downstream of the evaporation
stage and adapted to selectively remove, from the aerosol, residue
particles having electrical mobilities above a predetermined
threshold; and a concentration indicating component downstream of
the electrostatic selector, adapted to generate analyte
concentration information based on the residue particles received
from the selector.
23. The system of claim 22 wherein: the concentration indicating
component comprises a condensation particle counter, adapted to
cause growth of droplets through condensation of a working medium
onto the residue particles, then optically sense the resulting
droplets to generate indications of analyte concentrations.
24. The system of claim 22 wherein: the selector comprises an
electrical charging device adapted to apply a unipolar charge to
the residue particles, and an ion trap for removing particles
having electrical mobilities above a predetermined threshold.
25. The system of claim 22 wherein: the selector comprises a
neutralizer adapted to apply a predetermined charge distribution to
the residue particles, and a differential mobility analyzer
disposed downstream of the neutralizer to receive the charged
particles.
26. A device for generating an aerosol composed of multiple
droplets of a liquid, including: a housing forming a mixing chamber
having (i) a liquid entrance for receiving a sample liquid into the
chamber, (ii) a primary orifice having a first diameter for
receiving a pressurized gas into the chamber for merger with the
sample liquid to generate an aerosol composed of multiple droplets
of the sample liquid suspended in the gas, and (iii) a secondary
orifice having a second diameter for conducting the aerosol out of
the chamber; wherein the second diameter is less than a major
dimension of the mixing chamber taken in a direction substantially
perpendicular to an axis of the secondary orifice so as to restrict
flow out of the mixing chamber to generate a back pressure in
opposition to entry of the sample liquid and the pressurized gas
into the chamber.
27. The device of claim 26 wherein: the second diameter is less
than one half of the major dimension of chamber.
28. The device of claim 26 wherein: the second diameter is larger
than the first diameter.
29. The device of claim 26 wherein: the mixing chamber is
cylindrical and coaxial with the secondary orifice.
30. The device of claim 29 wherein: the primary orifice is coaxial
with the secondary orifice and the chamber.
31. The device of claim 29 wherein: the chamber has an axial length
less than a diameter of the chamber and greater than the second
diameter.
32. The device of claim 26 further including: an impactor coaxial
with the mixing chamber and spaced apart axially from the secondary
orifice downstream of the chamber, said impactor having a convex
upstream surface cooperating with a concave surface of the housing
to form a generally hemispherical path for conveying the aerosol
away from the chamber.
33. The device of claim 32 wherein: the impactor is movable axially
with respect to the housing to selectively adjust the axial spacing
between the impactor and the secondary orifice.
34. A device for optically detecting fine particles in an aerosol,
including: a housing having an inlet for receiving an aerosol
consisting essentially of substantially dry submicrometer residue
particles suspended in a carrier gas, and a passage for conveying
the aerosol in a steady stream through the housing along a
saturation region and along a supersaturation region downstream of
the saturation region; a holding component disposed along the
passage, adapted to contain a condensing medium in liquid form and
to release the condensing medium in vapor form as the aerosol is
conveyed along the passage; a first temperature maintenance device
disposed proximate the passage along the saturation region adapted
to maintain the saturation region substantially at a first
temperature; a second temperature maintenance device disposed
proximate the passage along the supersaturation region adapted to
maintain the supersaturation region substantially at a second
temperature different from the first temperature; a controller
operably associated with the temperature maintenance devices for
selectively setting the first temperature, the second temperature,
and a difference between the first and second temperatures, to
selectively vary a nucleation threshold at which the particles are
capable of serving as nuclei for condensation of the working medium
to grow droplets; and a droplet detector disposed at a sensing
location downstream of the passage and adapted to sense the
droplets resulting from said condensation as they pass the sensing
location.
35. The device of claim 34 wherein: the temperature maintenance
devices and the controller are configured to maintain the first
temperature within a first temperature range, and to maintain the
second temperature within a second temperature range that is higher
than the first temperature range.
36. The device of claim 34 wherein: the temperature maintenance
devices and the controller are configured to maintain the first
temperature within a first temperature range, and to maintain the
second temperature within a second temperature range that is lower
that the first temperature range.
37. The device of claim 34 wherein: the temperature maintenance
devices and controller are configured to maintain the first
temperature and the second temperature within respective first and
second substantially overlapping temperature ranges, whereby the
controller is operable alternatively to provide a first temperature
higher than the second temperature and a first temperature lower
than the second temperature.
38. The device of claim 34 further including: a working medium
holding component disposed along the passage, adapted to receive
and contain a working medium in liquid form and release the working
medium in vapor form as the aerosol is conveyed along the
passage.
39. The device of claim 34 wherein: said passage is cylindrical,
and the holding component comprises an annular porous liner
contiguous with and surrounded by a portion of the housing that
defines the passage.
Description
[0001] This application claims the benefit of priority based on
Provisional Patent Application No. 60/857,609, entitled "System for
Separating Non-volatile Analytes and Measuring Analyte
Concentrations," filed Nov. 7, 2006.
BACKGROUND OF THE INVENTION
[0002] The present invention relates to systems for measuring
minute concentrations of constituents dissolved in liquids, and
more particularly to systems that employ analyte separation and
aerosol generation to distinguish constituents and measure their
concentrations.
[0003] A variety of instruments are used for identifying and
measuring concentrations of solutes in liquid media. Separators can
employ any one of several analyte separation techniques, e.g.
liquid chromatography, high performance liquid chromatography
(normal or reversed phase), ion exchange chromatography and gel
permeation chromatography. Analyte separation involves moving
liquid and dissolved constituents, known as the mobile phase,
through a stationary phase, e.g. a stainless steel column or tube
packed with 5-10 mm silicon beads. As the liquid passes through the
column, different analytes become separated from one another due to
differing rates at which they travel through the stationary phase.
The liquid leaving the stationary phase is comprised of spatially
separated concentrations of the individual analytes. As a result, a
continuous measurement of the liquid stream yields a chromatogram
in which indications of relatively high concentration are
temporally separated from one another to suggest the presence of
different analytes. The chromatogram corresponds to the physical
separation of the analytes at the column exit, by recording the
different times at which different analyte concentrations leave the
column. The exit times are useful in identifying the analytes
involved.
[0004] Among the techniques for measuring analyte concentrations,
several involve generating aerosols based on the mobile phase
exiting the column. In one of these, known as evaporative light
scattering, a nebulizer is used to generate droplets of the
solution eluting from the separator column. The droplets dry as
they are carried by air or another gas, forming a stream of
non-volatile residue particles. As the particles are moved past a
laser beam, each particle that intersects the beam scatters light,
with larger particles scattering light at higher intensity. Thus,
the amplitude of a photodetector output provides a measurement of
particle size, which in turn provides an indication of analyte
concentration.
[0005] To enhance measurement of small analyte concentrations, the
particle stream can be directed through a condensation particle
counter (CPC), in which the particles travel through a region
saturated with the vapor of a working medium that condenses onto
the non-volatile residue particles that exceed a threshold
diameter, "growing" each particle into a considerably larger
droplet that is more easily detected by optical means.
[0006] In another technique, known as evaporative electrical
detection, the solution leaving a separator column is nebulized to
provide an aerosol stream, with the droplets again dried to provide
a particle stream. The particle stream is brought into a confluence
with a stream of ions, to apply a size-dependent electrical charge
to the non-volatile residue particles. An electrically conductive
filter collects the particles and generates an electrical current
indicative of analyte concentration.
[0007] While the systems are well suited for a variety of
applications, they are subject to difficulties that limit their
utility. One of these is the lack of sensitivity sufficient for
detecting and measuring extremely low analyte concentrations. As
environmental standards for exposure to various contaminants become
more stringent, and as product testing and manufacturing techniques
are directed to applications that require more accurate measurement
of constituents or have a reduced tolerance to certain
constituents, there is an ever increasing need to measure smaller
amounts of analytes with accuracy.
[0008] Another difficulty concerns bubble formation due to gasses
dissolved in the water or other liquid entering the nebulizer.
Bubbles can be formed when the liquid flow rate is below the
natural aspiration rate, with the liquid drawn into the nebulizer
at a pressure below atmospheric pressure. The bubbles eventually
break free and tend to disrupt residue concentration measurements
downstream of the nebulizer.
[0009] A further system problem, relating to the condensation
particle counter, concerns the use of butyl alcohol or similar
fluids with low vapor mass diffusivity for growing the residue
particles into droplets. Such liquids tend to be flammable, toxic,
and produce noxious odors. Frequently they are subject to health
and environmental regulations that restrict their use in indoor
environments. In addition, the liquids require equipment for
supplying, collecting and recirculating the liquid involved, and in
some cases for separating the liquid from water.
[0010] Another persistent problem, due to relatively long fluid
flow paths within and between the nebulizer and CPC, is the
relatively long time elapsed between a change in the concentrations
of analytes in a given liquid sample, and the detection of the
change. The longer paths allow more time for axial diffusion, which
ultimately has a negative impact on the instrument response.
[0011] Another difficulty with conventional condensation particle
counters is the limited dynamic range typical of many CPC designs,
due primarily to the increase in coincidence events that
accompanies increased particle concentration.
[0012] Accordingly the present invention has several aspects,
directed to one or more of the following objects: [0013] to provide
a system for detecting analyte concentrations based on droplet
growth and optical droplet sensing based on nonflammable and
nontoxic working media; [0014] to provide, in systems using
nebulizers to generate liquid sample aerosols, more rapid and
effective evaporation to dry the nebulizer output; [0015] to
provide a process for extending the dynamic range of a condensation
particle counter; [0016] to provide a nebulizer with a mixing
chamber better suited to generate finer aerosol droplets; [0017] to
provide an optical detector with enhanced flexibility for
determining particle nucleation thresholds and for accommodating a
wider variety of condensation media; and [0018] to remove smaller,
more volatile particles from the aerosol to enhance volatile
analyte detection.
SUMMARY OF THE INVENTION
[0019] In general, the invention is drawn to a system for analyzing
liquid samples including an analyte separator, an aerosol generator
for producing an aerosol stream of suspended particles derived from
the liquid output of the separator, and a particle sensing device
responsive to the particles for measuring analyte
concentrations.
[0020] One aspect of the invention is a system for measuring
analyte concentrations in liquids. The system includes an analyte
separation stage adapted to separate different analytes in a liquid
sample primarily into different regions within the liquid sample.
This produces a separation stage output in which a plurality of
different analytes are so separated. A nebulizing stage, downstream
of the analyte separation stage, is adapted to generate an aerosol
stream composed of droplets of the separation stage output
suspended in a carrier gas. An evaporation stage, downstream of the
nebulizing stage, is adapted to substantially evaporate the liquid
whereby the aerosol leaving the evaporation stage is composed of
residue particles of the different analytes suspended in the
carrier gas. A saturation stage, disposed downstream of the
evaporation stage, is maintained substantially at a first
temperature, and adapted to merge the aerosol with a working medium
vapor having a mass diffusivity higher than a thermal diffusivity
of the carrier gas, to substantially saturate the aerosol with the
working medium vapor. A condensation stage, disposed downstream of
the saturation stage, is maintained at a second temperature above
the first temperature, and adapted to merge further working medium
vapor with the substantially saturated aerosol to supersaturate the
aerosol and thereby cause droplet growth through condensation of
the working medium onto the residue particles. A sensing stage,
downstream of the condensation stage, is adapted to optically sense
the droplets and generate electrical signals useful in indicating
analyte concentrations.
[0021] In preferred systems, the saturation stage, condensation
stage and sensing stage are provided by a condensation particle
counter (CPC). These systems can use water, whose vapor has a
relatively high mass diffusivity, as the working or condensing
medium. Using water avoids the health and environmental concerns
associated with butyl alcohol and other perflourinated
hydrocarbons. This eliminates the need to supply, store and recover
such fluids, and to separate such fluids from the water.
[0022] When water is used as the working medium, the aerosol stream
is saturated with water vapor and proceeds to a condensing region
surrounded by wetted walls that are heated to provide a temperature
higher than that of the saturated aerosol stream. Maximum
supersaturation occurs at the center of the aerosol flow, given
that the water vapor and heat both travel radially inward, and the
mass diffusivity of water exceeds the thermal diffusivity of
air.
[0023] One advantage of using water as the working fluid in the CPC
is a substantially higher threshold at which spontaneous nucleation
(also called homogeneous nucleation) occurs, compared to a CPC in
which working medium is butyl alcohol. An improved coincidence
correction process also contributes to a considerably higher
permitted particle throughput rate. As a result of these
advantages, the concentration information is available virtually in
real time, and can encompass concentrations ranging from a single
part per trillion to ten parts per million in the single count
mode. If desired, a photometric mode can be employed to increase
the upper limit to over one part per thousand.
[0024] Another aspect of the invention is a system for analyzing
liquids. The system includes an analyte separator adapted to
separate different analytes in a liquid sample primarily into
different regions within the liquid sample, thereby to produce a
separator output in which a plurality of different analytes are so
separated. A nebulizer is fluid coupled to receive at least a
portion of the separator output, and to generate an aerosol
composed of droplets of the liquid suspended in a carrier gas. A
conduit structure is provided for guiding travel of the aerosol in
an aerosol stream away from a merger zone of the nebulizer. At
least a portion of the conduit structure is permeable to the
liquid, to promote an evaporation of the liquid and migration of
the vapor through that portion of the conduit to an exterior
thereof as the aerosol is conveyed along the conduit structure. The
aerosol leaving the conduit structure is composed of residue
particles of the analytes suspended in the carrier gas. A
concentration indicating component is disposed to receive the
aerosol leaving the conduit structure, and is adapted to indicate
analyte concentrations based on the residue particles received.
[0025] The concentration indicating component can comprise a
droplet growth component disposed downstream of the conduit
structure to receive the aerosol and merge the aerosol and a
working medium vapor, to supersaturate the aerosol and thereby
cause droplet growth through condensation of the working medium
onto the residue particles. In this case, the concentration
indicating component further includes a droplet sensing component,
downstream of the condensation component, adapted to optically
detect the droplets and generate electrical signals indicating
analyte concentrations.
[0026] The conduit structure can be incorporated into the
nebulizer, or can be provided as a length of tubing running between
the nebulizer and the droplet growth component, e.g. a condensation
particle counter. A preferred material for the tubing or nebulizer
interior wall is a copolymer available from E. I. duPont de Nemours
and Company of Wilmington, Del. under the brand name "Nafion." So
long as the ambient environment surrounding the tubing or nebulizer
is less humid than the aerosol, the liquid evaporates and migrates
outwardly through the wall in a process referred to as
"perevaporation," resulting in a rapid drying of the aerosol
stream. In addition to water, the Nafion tubing can remove
alcohols, amines and ammonia from the aerosol stream. The more
rapid removal of vapors can permit a considerably shorter aerosol
pathway between the nebulizer and the CPC. A key feature of the
Nafion conduit structure is that it facilitates vapor removal at
lower temperatures, for improved detection of volatile
analytes.
[0027] The nebulizer can incorporate a heating element just
downstream of the impactor, and an inlet downstream of the heating
element for admitting dry air to dilute the aerosol stream and
reduce the dew point of the liquid vapor.
[0028] Another aspect of the invention is a system for analyzing
liquid samples. The system includes an analyte separator adapted to
separate analytes in a liquid sample primarily into different
regions within the liquid sample, to produce a separator output in
which a plurality of different analytes are so separated. A
nebulizer is fluid coupled to receive at least a portion of the
separator output in a merger zone thereof, to generate an aerosol
composed of droplets of the liquid suspended in a carrier gas. An
evaporation stage, downstream of the nebulizer, is adapted to
substantially evaporate the liquid whereby the aerosol leaving the
evaporation stage is composed of residue particles of the different
analytes suspended in the carrier gas. An electrostatic selector is
disposed downstream of the evaporation stage and adapted to
selectively remove, from the aerosol, residue particles having
sizes less than a predetermined threshold. A concentration
indicating component downstream of the selector is adapted to
generate analyte concentration information based on residue
particles received from the selector.
[0029] The concentration indicating component can comprise an
optical particle counter adapted to cause growth of droplets
through condensation of a working medium onto the residue
particles, then optically sense the resulting droplets to generate
indications of analyte concentrations.
[0030] In one version of the system, the electrostatic selector
comprises a unipolar electrical charging device, e.g. a corona
discharge element generating multiple ions to merge with the
aerosol and charge the particles. This is followed by an ion trap
selectively biased to remove the ions and particles having higher
electrical mobilities. In another version of the system, the
selector comprises a neutralizer which applies a bipolar charge to
the aerosol particles, followed by a differential mobility analyzer
(DMA). An aspect of this version is that the DMA can be used to
remove residue particles on both sides of a desired range of
particle electrical mobilities, in effect setting an upper limit as
well as a lower limit for particle retention. Either of these
versions can be used to improve the response to volatile analytes.
In addition, analyte concentration information can be generated by
means other than optical particle counting.
[0031] Yet another aspect of the invention is a device for
generating an aerosol composed of multiple droplets of a liquid.
The device includes a housing forming a mixing chamber having (i) a
liquid entrance for receiving a sample liquid into the chamber,
(ii) a primary orifice having a first diameter for receiving a
pressurized gas into the chamber for merger with the sample liquid
to generate an aerosol composed of multiple droplets of the sample
liquid suspended in the gas, and (iii) a secondary orifice having a
second diameter for conducting the aerosol out of the chamber. The
second diameter is less than a major dimension of the mixing
chamber taken in a direction substantially perpendicular to an axis
of the secondary orifice, so as to restrict flow out of the mixing
chamber to generate a back pressure in opposition to entry of the
sample liquid and the pressurized gas into the chamber.
[0032] In contrast to previous nebulizers in which the chamber exit
is simply open to the downstream components with a diameter equal
to that of the chamber, the exit orifice in the present nebulizer
has a diameter less than that of the chamber, and more preferably
less than half the chamber diameter. The diameter reduction
provides a constriction which produces a higher kinetic energy
mixing of the gas and separator eluent in the merger zone. As a
result, the nebulizer generates smaller droplets. The secondary
orifice also helps direct the aerosol towards the impactor raising
the impactor efficiency
[0033] Another factor reducing droplet size is a close axial
positioning of an impactor, just downstream of the secondary
orifice. The more closely spaced impactor removes a greater
proportion of the larger droplets, reducing baseline concentration
(noise) for improved dynamic range in generating analyte
concentration data.
[0034] In a preferred version of the nebulizer, the impactor axial
spacing from the secondary orifice is adjustable through movement
of the impactor. For example, a threaded mounting of the impactor
to the nebulizer frame allows axial position adjustment by turning
the impactor about its longitudinal axis. The average size of
droplets in the aerosol leaving the nebulizer can be increased or
decreased by respectively enlarging or reducing the axial spacing
between the secondary orifice and the impactor.
[0035] The droplet size also can be adjusted by changing or
selecting the secondary orifice. Reducing the diameter of the
secondary orifice is believed to increase back pressure and reduce
droplet size. It has been found useful to provide a secondary
orifice with a diameter larger than that of the primary orifice.
The ratio of the secondary orifice diameter to the primary orifice
diameter can range from slightly above one, to about two in
versions that incorporate a secondary orifice.
[0036] A further aspect of the invention is a device for optically
detecting fine particles in an aerosol. The device includes a
housing having an inlet for receiving an aerosol consisting
essentially of substantially dry submicrometer residue particles
suspended in a carrier gas, and a passage for conveying the aerosol
in a steady stream through the housing along a saturation region
and along a supersaturation region downstream of the saturation
region. A holding component, disposed along the passage, is adapted
to contain a condensing medium in liquid form and to release the
condensing medium in vapor form as the aerosol is conveyed along
the passage. A first temperature maintenance device, disposed
proximate the passage along the saturation region, is adapted to
maintain the saturation region substantially at a first
temperature. A second temperature maintenance device, disposed
proximate the passage along the supersaturation region, is adapted
to maintain the supersaturation region substantially at a second
temperature different from the first temperature. A controller
operably associated with the temperature maintenance devices for
selectively setting the first temperature, the second temperature,
and a difference between the first and second temperatures, to
selectively vary a nucleation threshold at which the particles are
capable of serving as nuclei for condensation of the working medium
to grow droplets. A droplet detector, disposed at a sensing
location downstream of the passage, is adapted to sense the
droplets resulting from said condensation as they pass the sensing
location.
[0037] In detectors (e.g. condensation particle counters) that use
working media with mass diffusivities higher than the thermal
diffusivity of air or another gas, the controller and temperature
maintenance devices are configured to maintain the second
temperature within a higher range than that of the first
temperature, for a supersaturation region that is warmer than the
saturation region. Conversely, in a CPC using lower mass
diffusivity media such as butyl alcohol, the first temperature is
maintained within the higher range to insure that the
supersaturation region is cooler than the saturation region. In
either event, the difference between the first and second
temperatures can be selectively adjusted to influence droplet
nucleation and growth. For example, increasing the difference
between the first and second temperatures lowers the nucleation
threshold, tending to increase the number of particles sensed and
therefore counted.
[0038] In another version of the device, the first and second
temperature ranges are substantially overlapping, in which case the
controller can be used to select either the saturation region or
the supersaturation region as the warmer region.
[0039] Thus, analyte measuring systems configured according to the
present invention generate more reliable concentration information
in virtually real time and over a wider range of residue
concentrations.
IN THE DRAWINGS
[0040] For a further understanding of the above and other features
and advantages, reference is made to the following detailed
description and to the drawings, in which:
[0041] FIG. 1 is a block diagram of a liquid chromatography system
configured in accordance with the present invention and employing
high performance liquid chromatography;
[0042] FIG. 2 is a schematic view of part of the system;
[0043] FIG. 3 is a sectional side elevation of a nebulizer of the
system;
[0044] FIG. 4 is a sectional view taken along the line 4-4 in FIG.
3;
[0045] FIG. 5 is an enlarged view showing part of FIG. 4;
[0046] FIG. 6 is a sectional elevation of a condensation particle
counter of the system;
[0047] FIG. 7 is a graphical representation of certain electrical
signals used in of the system;
[0048] FIGS. 8 and 9 illustrate alternative embodiment condensation
particle counters used with the system;
[0049] FIGS. 10, 11 and 12 illustrate portions of alternative
systems that incorporate particle selection features;
[0050] FIG. 13 is a schematic view of an alternative arrangement
for drying an aerosol as it is conveyed from a nebulizer mixing
region;
[0051] FIG. 14 schematically illustrates part of an alternative
system with a "mixing type" condensation particle counter; and
[0052] FIG. 15 illustrates part of an alternative system
condensation particle counter incorporating photometric particle
detection.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0053] Turning now to the drawings, there is shown in FIG. 1 a
diagram of a high performance liquid chromatography (HPLC) system
16 for identifying and measuring concentrations of non-volatile
residue constituents dissolved in water or another liquid. The
system includes a high performance liquid chromatography pump 18
for supplying water or another solvent as a carrier liquid (mobile
phase) through a conduit 20 at a predetermined constant flow rate,
e.g. 1 milliliter per minute. An injection valve 22 along conduit
20 is coupled to a syringe 24 containing a liquid sample and
operable in stepped fashion to introduce substantially
instantaneous injections of the liquid sample into the carrier
liquid stream. The injections do not undergo any substantial mixing
with the carrier liquid, but instead form plugs of the liquid
sample that remain substantially separate from the carrier liquid.
The liquid sample includes a base liquid such as water,
acetonitrile (CH.sub.3CN), or alcohols, along with non-volatile
residue and other analytes or constituents dissolved in the base
liquid.
[0054] Beyond valve 22, the carrier liquid (mobile phase) and plugs
travel at the predetermined flow rate into a high performance
liquid chromatography column 26. Column 26 includes a stainless
steel tube loaded with a stationary phase, e.g. silicon beads as
noted previously. The liquid sample plugs move through column 26
along with the carrier liquid. As each plug proceeds through the
column, different constituents travel through the column at
different rates, depending largely on their chemical attraction to
the stationary phase as compared to their chemical attraction to
the mobile phase. Materials having stronger interaction with the
stationary phase tend to travel more slowly, as compared to
materials having stronger interactions with the mobile phase. As a
result, different constituents tend to become concentrated in
different regions of each liquid sample plug as it travels through
column 26. Consequently, each plug as it leaves column 26 has
distinct regions with different concentrations of different
constituents, separated from one another temporally as well as
spacially since the with liquid sample is moving at the
predetermined flow rate as it leaves the HPLC column.
[0055] A conduit 28 transfers either all or a predetermined
fraction of the HPLC column output to a pneumatic nebulizer 30. The
nebulizer also receives air, nitrogen or another gas under pressure
from a pressurized gas source 32. Within nebulizer 30, the liquid
sample and compressed gas are merged to generate an aerosol
including droplets of the liquid sample suspended in the gas.
[0056] Most of the liquid provided to nebulizer 30, over 95 percent
and typically closer to 100 percent, is not used to form droplets,
but instead is drained from the nebulizer through a waste conduit
33.
[0057] The aerosol stream is dried to reduce the aerosol droplets
to suspended residue particles. Then the aerosol stream is provided
to a condensation particle counter (CPC) 34. As the aerosol travels
through the CPC, it is first saturated with water from a working
fluid supply 36. Then, the aerosol is channeled through a
condensation or supersaturation region in which the residue
particles act as nuclei for condensation. The residue particles
"grow" into considerably larger droplets that are optically
detected and counted to generate non-volatile residue concentration
information. The concentration information is provided to a
microprocessor 38. The microprocessor provides the information to a
video display terminal 40 to generate a continuously updated record
of non-volatile residue concentrations in the liquid sample.
[0058] CPC 34 includes an exit 44 through which the aerosol is
drawn by a pump 120 (FIG. 2) out of the CPC. In addition, excess
aerosol not used in the particle count and excess water are
exhausted as noted in connection with FIGS. 2 and 6.
[0059] FIG. 2 illustrates in more detail the portion of system 16
downstream of HPLC column 26. The liquid output of HPLC column 26
is provided through a bulkhead fitting 46 into a merger zone 48 of
nebulizer 30, at a flow rate determined by the flow rate through
the HPLC column and the fraction of the column output directed to
the merger zone. In system 16, a suitable flow rate is one
milliliter per minute.
[0060] Air from source 32 is provided through a solenoid valve 50
to a regulator 52 and measured using a pressure transducer 54.
Downstream, the air passes through a high efficiency particle air
(HEPA) filter 56, and then is supplied via an entrance 58 to merger
zone 48 at a pressure of 30 psi and a flow rate of 0.6 liters per
minute through a conduit 60. Air also is provided to an aerosol
conditioning zone 62 of nebulizer 30 through a conduit 64. Conduit
64 includes either a valve or a control orifice 66 for limiting the
air flow to a rate of about 2.7 liters per minute.
[0061] Nebulizer 30 includes a reservoir 68 in fluid communication
with the merger zone. The reservoir collects most of the mobile
phase supplied through conduit 28, i.e. the liquid not used to form
the aerosol droplets. A pump 70 is coupled to the reservoir for
evacuating the waste liquid from nebulizer 30.
[0062] FIGS. 3-5 illustrate nebulizer 30 in more detail. The
inclined orientation shown is advantageous for liquid drainage and
evacuation, although not critical. A housing of the nebulizer has
several integrally coupled sections, including a stainless steel
housing section 72 that encloses merger zone 48, a steel housing
section 74 forming the aerosol conditioning zone, and a housing
section 76 providing the reservoir. Housing section 72 supports a
fitting 78 for receiving the air or other compressed gas from
conduit 60. This housing section also supports an impactor 80,
through a threaded engagement that permits adjustment of the axial
spacing between impactor 80 and merger zone 48.
[0063] With reference to FIG. 4, housing section 72 further
supports a thermoelectric device 82 that functions to maintain a
stable temperature of about 30.degree. C. in the vicinity of merger
zone 48. More particularly, the thermoelectric device extracts heat
from housing section 72 and transfers it to a heat sink 84. The
thermoelectric device also may function as a heater for the
nebulizer. The constant temperature promotes consistent droplet
formation. Housing section 72 further supports bulkhead fitting 46,
which secures conduit 28 used to transfer the sample liquid from
HPLC column 26 to merger zone 48.
[0064] As best seen in FIG. 5, merger zone 48 takes the form of a
cylindrical chamber in a Teflon orifice housing 73. A sapphire
orifice plate 86 defines an entrance or primary orifice to receive
pressurized gas into the chamber from conduit 60. A sapphire
orifice plate 88 defines an exit or secondary orifice through which
the merged liquid and gas leave the chamber. In addition, a liquid
receiving entrance 90 conducts the sample liquid into the
chamber.
[0065] In one suitable version of nebulizer 30, primary orifice 86
has a diameter of 0.006 inches, and secondary orifice 88 has a
diameter of 0.008 inches. The chamber has a diameter of 0.020
inches, and an axial length, i.e. space in between orifice plates
86 and 88, of 0.020 inches.
[0066] More generally, the secondary orifice diameter is larger
than the primary orifice diameter, yet less than the diameter of
the cylindrical chamber. As compared to prior devices in which
there is no secondary orifice and the chamber is simply open at the
exit end, there is a back pressure due to the secondary orifice
which increases the feed pressure to the merger zone and results in
a higher kinetic energy mixing of the liquid and compressed gas.
This advantageously results in smaller sample liquid droplets in
the aerosol leaving the merger zone.
[0067] As the size of the secondary orifice is reduced, the droplet
size is reduced and the back pressure is increased. When the sample
liquid is water, it has been found satisfactory to form the
secondary orifice and the primary orifice at a diameter ratio of 2
to 1 as indicated by the diameters given above. For a sample liquid
with a boiling point lower than water, the preferred diameter ratio
is closer to 1, yet the secondary orifice remains larger than the
primary orifice.
[0068] The higher energy in the merger zone more effectively breaks
up the liquid. The secondary orifice also appears to improve the
efficiency of the impactor downstream. The ratios of primary and
secondary orifice diameters can be selected to vary the pressure at
the liquid entrance to the merger zone, relative to atmospheric
pressure. Depending on the diameter ratio, air inlet pressure and
liquid flow rate (as determined by the HPLC pump), the liquid
pressure can be adjusted from below atmospheric pressure to a
pressure nearly equal to the inlet air pressure. Keeping the liquid
near atmospheric pressure is advantageous for reducing measurement
errors due to outgassing.
[0069] As seen in FIG. 5, impactor 80 is disposed coaxially with
merger zone 48, spaced apart in the axial direction from orifice
plate 88. The impactor cooperates with housing section 72 to form a
thin, somewhat hemispherical path to accommodate the flow of air
and droplets beyond the merger zone. The smaller droplets tend to
follow the air flow, while the larger droplets tend to collide with
impactor 80 and are removed from the aerosol stream. Thus, the
aerosol moving into conditioning zone 62, upwardly and to the right
as viewed in FIG. 3, includes only those droplets below a size
threshold determined largely by the axial spacing between secondary
orifice 88 and impactor 80. The size threshold is increased by
increasing the axial spacing, and reduced by moving the impactor
closer to orifice plate 88.
[0070] The droplets impinging upon impactor 80 may remain on the
impactor momentarily, but eventually descend to reservoir 68 to be
removed from the nebulizer as needed through pump 70. If desired,
impactor 80 may be formed of sintered metal to provide a porous
structure that more effectively prevents the larger, impacting
droplets from interfering with the aerosol flow.
[0071] As the aerosol stream proceeds along conditioning zone 62,
it is heated by an electrical heating element 92 to a temperature
of 35-100.degree. C., depending on the mobile phase and analyte
volatility. This evaporates the sample liquid, transforming the
aerosol into a particle suspension rather than a droplet suspension
by the time it reaches CPC 34. A temperature sensor 94 at the end
of conditioning zone 92 is operable in conjunction with the heating
element to maintain the desired temperature within the conditioning
zone. The aerosol is merged with the air flow from conduit 64
through a fitting 96 to provide a diluted aerosol flow of about 3.3
liters per minute to CPC 34. Dilution reduces the dew point to
sustain droplet evaporation and reduces the aerosol particle
concentration as the aerosol leaves the nebulizer through a fitting
98.
[0072] With reference to FIG. 2, the aerosol proceeds from
nebulizer 30 to an aerosol mixer 100, and then to condensation
particle counter 34.
[0073] A secondary gas may be introduced into nebulizer 30 at a
location upstream of the nebulization region as indicated at 99
(FIG. 2). The secondary gas sweeps dead space in the nebulization
region resulting in a faster response, reduced axial diffusion, and
less smearing of the output due to mixing.
[0074] FIG. 6 illustrates condensation particle counter 34 in more
detail. The CPC includes a droplet growth column 102 including a
substantially rigid cylindrical outer wall 104 and a porous
cylindrical inner liner or wick 106 formed of a ceramic. Wick 106
is adapted to receive and hold water or another condensation
medium, and thereby provide vapor to an internal passage 108
surrounded by the wick. If desired, wick 106 can be mounted
removably to facilitate inspection and convenient replacement. A
lower, saturation region 110 of passage 108 is maintained at a near
ambient temperature, e.g. at 20.degree. C. A thermoelectric device
111 is optionally used to maintain the saturation region
temperature. A heating element 112 is used to maintain an upper,
droplet growth region 114 of the chamber at an elevated
temperature, e.g. 60.degree. C. As the aerosol from nebulizer 30
proceeds upwardly through passage 108, it becomes saturated along
region 110. As the aerosol travels through region 114, it becomes
supersaturated with the vapor. All particles in the aerosol having
at least a threshold size become nucleation sites for droplet
growth due to water condensation.
[0075] As the particles proceed upwardly through growth region 114,
two counteracting phenomena are at work. First, due to the elevated
temperature the wetted wick generates increased water vapor, which
travels radially inward away from the wick toward the center of
passage 108. This of course promotes condensation onto the
particles. Second, as the aerosol is heated, the higher temperature
tends to discourage condensation. However, because of the
relatively high mass diffusivity of water vapor, the water vapor
reaches the center of passage 108 more quickly than the heat.
Consequently the particles and their immediately adjacent air, even
while being warmed, remain sufficiently cool for supersaturation
and the resulting condensation and droplet growth.
[0076] A laser diode 116 and photodetector 118 are disposed above
droplet growth column 102 proximate the aerosol stream. Each
droplet alters or interrupts light transmission to the
photodetector to generate an analog electrical pulse. The pulses
are digitized and provided to processor 38, and the pulse count
yields the non-volatile residue concentration.
[0077] With reference to FIG. 2 as well as FIG. 6, a pump 120 draws
the aerosol out of CPC 34 through a flow metering orifice 121 and
provides it to a waste outlet 122, along with a dilution air flow
of about 0.8 liters per minute from a conduit 123. A sample flow of
the aerosol in the range of 100-300 milliliters per minute is
provided to passage 108 from a CPC inlet 125. Excess aerosol flows
through an exhaust exit 127 to waste outlet 122. The CPC receives
the water or other condensation medium from working fluid supply
36, preferably a 250-500 cc bottle.
[0078] As seen in FIG. 6, CPC 24 includes a reservoir 124 fluid
coupled to the working fluid supply through a solenoid valve 126.
Water is provided from reservoir 124 to wick 106, to insure that
the wick remains wetted to provide water vapor along the saturation
and growth sections. The solenoid valve normally is closed. When a
level sensor 128 in the reservoir senses that the water level in
the reservoir has receded below a predetermined threshold, it opens
valve 126 to replenish the water supply in the reservoir. Reservoir
124 can be provided with a fitting for draining excess water if
desired.
[0079] As noted previously, the use of water as the condensing
fluid avoids health and environmental concerns associated with
butyl alcohol and other perflourinated hydrocarbons in CPC 34.
[0080] A feature of CPC 34 is that when the particulate
concentration increases, the sensitivity is reduced. One factor
contributing to this result is that as more particles within a
given volume serve as nucleation sites, the heat generated by
condensation lowers the supersaturation ratio. This in turn raises
the threshold (minimum particle size) for particle nucleation,
improving the overall dynamic range of the detector. Another, more
prominent factor is the increase in coincidence events with
increased concentration. As each droplet intersects the coherent
energy beam from diode 116 to generate the corresponding pulse, it
also creates a time interval during which any other droplet also
intersecting the beam is prevented from generating a pulse, and
thus goes undetected.
[0081] With reference to FIG. 7, the signal generated by a droplet
intersecting the beam is represented by an analog pulse 130. The
broken line labeled "V.sub.DIS" represents a threshold voltage for
droplet detection. More particularly, the voltage V.sub.DIS is
provided to the negative input of a comparator amplifier 132. The
sensed analog voltage is provided to the positive input of the
amplifier. The output of amplifier 132 is a series of digital
pulses corresponding to the analog pulses. For example, digital
pulse 134 has a pulse width "t" corresponding to the discriminator
time for pulse 130, i.e. the time interval during which the voltage
of pulse 130 remains above the discriminator voltage.
[0082] The digital pulses produced by amplifier 132 are provided to
a resistance capacitance network having a resistance R and a
capacitor having a capacitance C. The capacitor is charged during
each digital pulse, i.e. whenever the output of amplifier 132 is at
the high level. The RC network generates an output V.sub.DT which
increases with the charge to the capacitor. Accordingly, voltage
V.sub.DT represents the total discriminator time for a given
sampling interval. Concentration is calculated every 0.10
seconds.
[0083] The time constant for the RC circuit is preferably about
equal to the signal sampling time, and considerably greater (by
orders of magnitude) than the expected widths of the digital
pulses.
[0084] There is a tendency of V.sub.DT to underestimate the actual
dead time, and the tendency becomes stronger as particle or droplet
densities increase. In accordance with the present invention,
system 16 is tested with challenges of known particle sizes and
concentrations to determine the relationship between particle
concentration and network output V.sub.DT to determine a correction
function or constant. The resulting constant corrects V.sub.DT to
particle or droplet concentrations, and is stored to microprocessor
38. Then, in conjunction with providing network output V.sub.DT to
the microprocessor, the stored function is applied to the voltage
to determine particle concentrations. In general, the function is
used to determine concentration based on a numerical particle count
divided by a product of an adjusted sampling time and the flow
rate, which is proportional to the concentration of non-volatile
analyte exiting HPLC column 26. The adjusted sampling time is
determined by subtracting the discriminator time from the actual
sampling time. Thus, a correction factor is applied to the
numerical count to yield a higher concentration than the count
otherwise would indicate, taking into account the factors noted
above.
[0085] In one preferred version of the HPLC system, the
condensation particle counter can be tuned to exhibit a desired
threshold size for droplet growth and a desired droplet growth
rate. FIG. 8 schematically shows a CPC 136 with a thermoelectric
device 138 surrounding a droplet growth column 140 along a
saturation region 142, and a heater 144 surrounding the growth
column along a droplet growth region 146. A controller 148 is
operable to individually set the temperatures of devices 138 and
144, thus to set the temperatures in the respective regions.
[0086] Controller 148 is used to adjust a saturation region
temperature T.sub.S and a growth region temperature T.sub.G with
respect to each other, as well as individually. An increase in the
difference between temperatures T.sub.G and T.sub.S lowers the
nucleation threshold, and thus increases the number of particles
counted by the CPC for any given aerosol exhibiting a range of
particle sizes. In addition, the rate of droplet growth can be
increased by raising both temperatures T.sub.G and T.sub.S by a
given amount, retaining the difference between these temperatures.
This adjustment, likewise, tends to increase the particle count
resulting from a given aerosol sample.
[0087] In accordance with another aspect of the invention, the HPLC
system includes a condensation particle counter equipped to use a
variety of different working or condensing liquids, for example
both water and butyl alcohol. Effective use of both of these fluids
requires a reversal in the saturation region temperature T.sub.S
and growth region temperature T.sub.G.
[0088] To this end, FIG. 9 shows a CPC droplet growth column 150
including a saturation region 152 and a droplet growth or
condensation region 154 downstream of the saturation region. An
upstream thermoelectric device 156 surrounds the growth column
along saturation region 152. A downstream thermoelectric device 158
surrounds the column along the condensation region. A controller
160 is operably coupled to the thermoelectric devices to determine
temperatures T.sub.S and T.sub.G along the saturation and growth
regions, respectively.
[0089] As noted above, the mass diffusivity of water exceeds the
thermal diffusivity of air. As a result, particles traveling
through droplet growth region 154 are being warmed, yet can serve
as droplet growth sites because they remain sufficiently cool to
condense the surrounding water vapor.
[0090] In contrast, the vapor of butyl alcohol has a mass
diffusivity lower than the thermal diffusivity of air. In this
case, the saturating temperature T.sub.S is set higher than the
droplet growth region temperature T.sub.G. In this arrangement,
although the tendency of the wick to generate vapor is reduced
along the droplet growth region, this is overcome by the reduced
temperature of the particles, which increases their capacity to
serve as condensation sites.
[0091] According to several alternative liquid chromatography
systems, the dried aerosol is selectively modified to remove
smaller more volatile components. For example, FIG. 10 illustrates
part of an HPLC system 160 in which a filter assembly 162 is
positioned along the aerosol path between a nebulizer 164 and a
condensation particle counter 166. The filter assembly incorporates
a series of diffusion screens 168 designed to entrap particles with
high diffusion coefficients, i.e. particles sufficiently small to
be driven in irregular paths due to random collisions with gas
molecules. While larger particles tend to travel linearly through
the diffusion screens, smaller particles tend to collide with the
screen wires and are retained by surface-attractive forces.
[0092] The number of diffusion screens 168 can be changed to
selectively alter the size distribution of the aerosol particles
leaving filter assembly 162. In particular, increasing the number
of screens captures and removes a larger proportion of the aerosol
particles from the aerosol stream. As a result of this selective
filtration, CPC 166 produces an increased signal response for
volatile components.
[0093] FIG. 11 schematically illustrates part of another
alternative HPLC system 170 configured to electrostatically remove
smaller particles from the aerosol stream between a nebulizer 172
and condensation particle counter 174. In this system, a conduit
176 conveys the dried aerosol away from the nebulizer towards a
merger zone 178 which also receives a carrier gas conveyed by a
conduit 180. A corona discharge needle 182, biased to a voltage +V,
applies a unipolar charge to the carrier gas, in this case creating
positive ions. At merger zone 178, the aerosol and the ionized gas
combine to form positively charged reside particles and positive
ions that travel downstream along a conduit 184.
[0094] An ion trap 186, disposed along conduit 184, includes an
electrically grounded conductive cylindrical wall 188 and a
conductive rod 190 electrically isolated from the wall. Rod 190 is
negatively biased to a voltage -V to create an electrical field
between the rod and the surrounding wall.
[0095] As the aerosol passes through ion trap 186, the electrical
field causes the ions and the smaller particles, i.e. the higher
electrical mobility components, to precipitate onto wall 188. The
larger particles tend to continue flowing downstream toward CPC
174.
[0096] The ion trap voltage -V can be adjusted to selectively
increase or decrease the maximum diameter of particles removed from
the aerosol by the ion trap. Also, it is to be understood that
various modifications can be employed to yield the same result e.g.
reversing the polarities of rod 190 and corona discharge needle
182, biasing wall 188 in addition to or in lieu of rod 190,
etc.
[0097] FIG. 12 illustrates another alternative approach for
electrostatically removing selected particles from the dried
aerosol stream before growing droplets, in particular a liquid
chromatography system in which a dried aerosol stream emerging from
a nebulizer 192 is conveyed through a charging device 194, then
through a differential mobility analyzer (DMA) 196 before reaching
a condensation particle counter 198.
[0098] Charging device 194 may employ a radioactive charger, or
oppositely charged unipolar elements such as corona discharge
needles. In either event, aerosol entering DMA 196 has a uniform
charge distribution. In a further alternative approach, a unipolar
charger is used in lieu of device 194.
[0099] The DMA guides the aerosol along a path between a
cylindrical outer wall and an electrically charged rod centered and
coaxial with the wall. Ions and charged particles with polarities
opposite to that of the rod are attracted toward to rod. Higher
mobility components precipitate along an upstream region of the
rod. Particles with low electrical mobilities precipitate along a
downstream region of the rod. Components having electrical
mobilities within a selected range between "high" and "low" travel
through a slot in the rod between the upstream and downstream
regions. The portion of the aerosol containing these midrange
components is provided to CPC 198. Thus, in addition to removing
small particles, this approach entails removing larger particles as
well, to confine the analysis to a particular desired range of
particle sizes.
[0100] FIG. 13 illustrates part of a further alternative system
directed to reducing the length of the aerosol flow path between a
nebulizer 200 and a condensation particle counter 202. Nebulizer
200 is similar to the previously discussed nebulizers in that a
sample liquid and a pressurized gas are provided through respective
entrance conduits 204 and 206 to a merger zone 208, from which the
resulting aerosol is conducted downstream through a conduit
210.
[0101] In a departure from the previous nebulizers, conduit 210 is
formed by a cylindrical wall 212 that is permeable to the test
liquid and adapted to transfer the test liquid vapor to the ambient
environment surrounding nebulizer 200 by a process known as
perevaporation. To enhance the process, it is desirable to maintain
a low relative humidity environment about the nebulizer, although
transfer of the sample liquid vapor continues so long as the
environment is less humid than the aerosol inside conduit 210.
[0102] While not illustrated in FIG. 13, a heating element can be
disposed along conduit 210 to promote evaporation as in previous
embodiments. In either event, evaporation of the sample liquid
proceeds at a more rapid rate due to the transfer of the vapor to
the outside environment. A satisfactory material for wall 212 is
sold by E. I. duPont de Nemours and Company of Wilmington, Del.
under the brand name "Nafion". While removing water vapor in this
fashion, conduit 210 is similarly adapted for rapid removal of
other liquids such as alcohols, amines, and ammonia. Due to the
more rapid removal of these liquids, conduit 210 can provide a
considerably shorter aerosol path from the nebulizer to the CPC,
and yet provide substantially dry residue particles to the CPC for
droplet growth. Conduit 210 can be built into the nebulizer as
illustrated, or alternatively can be provided as a separate
component along the aerosol path from a nebulizer to a condensation
particle counter.
[0103] By allowing the test liquid paper to permeate through wall
212 to the ambient environment, conduit 210 tends to lower the dew
point of the aerosol. This promotes evaporation without the need to
raise the aerosol temperature. The ability to dry the aerosol
without heating it considerably enhances the capacity of the system
to measure more volatile analytes.
[0104] FIG. 14 illustrates part of an alternative HPLC system in
which a conduit 214 conveys a substantially dried aerosol from a
nebulizer 216 to an optical particle counter 218. A conduit 220
conveys pressurized air or another pressurized gas to the optical
particle counter. A saturator 222, disposed along conduit 220,
contains water, butyl alcohol or another working medium in liquid
form. A heater 224 along the saturator raises the temperature of
the gas, and at the same time promotes evaporation of the working
medium to substantially saturate the gas.
[0105] Upstream of optical particle counter 218 is a merger region
fluid coupled to conduits 214 and 220 for combing the aerosol and
the saturated gas. Due to its lower temperature as compared to the
saturated gas, the aerosol upon merger tends to cool the gas,
leading to supersaturation and condensation of the working medium
onto the aerosol particles. This leads to the growth of droplets,
which are optically sensed as before.
[0106] FIG. 15 illustrates a feature that can be incorporated into
any of the preceding condensation particle counters to enhance the
dynamic range of the system involved. As represented schematically,
a condensation particle counter 226 has a droplet growth column 228
disposed to receive dried particles of an aerosol and, through
condensation of a working medium, provide as its output an aerosol
including suspended droplets 230.
[0107] Downstream, a laser diode 232 generates a laser beam 234
that intersects the aerosol stream. Light scattered by droplets 230
is received by a photodetector 236 configured to sense droplets 230
individually, providing a signal via a line 238 to a processor 240
each time one of the droplets traverses a viewing volume determined
by the intersection of laser beam 234 and the aerosol path.
Photodetector 236 further is configured to sense multiple droplets
simultaneously by generating an electrical signal having an
amplitude proportional to the amplitude of light scattered in
concert by multiple particles. This signal is provided to the
processor via a line 242.
[0108] Photodetector 236 provides for high accuracy at low analyte
concentrations, based on the droplet count over a given sampling
time. When an analyte concentration becomes too high for individual
counting, processor 240 is configured to use the active analyte
concentration input from line 240, i.e. the photometric
measurement.
[0109] Thus, in accordance with the present invention, a system for
monitoring analyte concentrations in water and other liquids
generates more reliable information virtually in real time, to
facilitate more effective management of processes that depend on
analyte identification and measurement. The system can be tuned to
adjust nucleation thresholds and droplet growth rates, and accounts
for coincidence episodes and thermal depletion to extend the useful
range for generation of concentration data based on particle
counts.
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